Data from this laboratory supports the following concepts: 1. The urinary bladder of the toad can acidify urine, produce ammonium ion from ammonia precursors, and excrete ammonium ion. 2. The rate of acidification of urine by the bladder is increased in response to either a metabolic or a respiratory acidosis. 3. The rate of excretion of ammonium ion is increased in response to a metabolic acidosis. 4. Factors prepared from plasma of toads in metabolic acidosis can increase the rate of H ion and ammonium ion excretion in bladders from toads in normal acid-base balance, and these factors are not H ion, HCO minus 3, or CO2 in solution. 5. These same effects can be produced by factors prepared from plasma of acidotic dogs. 6. These factors are not found in plasma of toads or dogs in normal acid-base balance. Paired hemibladders mounted between lucite chambers were used to obtain the above data. One hemibladder is a control hemibladder and the other hemibladder from the same toad is the experimental hemibladder. The rate of excretion of H ion and/or ammonium ion and/or the rate of formation of ammonium ion are determined on each hemibladder. Using these methods we then propose to determine a dose-response curve for the factor which stimulates H ion excretion, and evaluate the efficiency of the extraction procedures presently used or obtaining it. We propose a method to determine whether the observations of an increase in H ion excretion and an increase in ammonium ion excretion observed are due to different factors in plasma. In addition, we hope to determine if these factor(s) come from the adrenal gland of the animal. We will also determine if this is a cellular adaptation in the bladder during acidosis that allows the bladder to excrete more H ion when the animal is in metabolic acidosis.